Mass spectrometry (MS) is an established method for the analysis of many biochemical samples such as, for example, protein and peptide samples in proteomics research. Whilst MS may be used directly on simple samples, in cases of complex samples consisting of a large number (possibly thousands) of components (e.g. proteins), the samples are typically subject to a separation process prior to the MS analysis, e.g. by liquid chromatography (LC). Prior to the LC process of the LC/MS analysis, a sample preparation is often performed that may involve some form of sample separation, such as a purification and/or concentration step.
Solid phase extraction (SPE) is a technique for preparing samples prior to LC. The technique comprises using a sorbent held in a column commonly known as a trap column, often in the form of a disposable cartridge or tip, to purify and/or concentrate samples prior to analysis. Disposable SPE cartridges or tips that can be disposed of after a single use have the advantage that they avoid a step of cleaning them before the next use. The use of SPE followed by LC is herein termed an SPE-LC method.
Attempts have been made to increase throughput in SPE-LC by using an automated system to interface the SPE columns to the LC system. Such systems are described in U.S. Pat. No. 7,409,880 and Hørning et al, International Journal of Mass Spectrometry 268 (2007) 147-157. A multiplicity of SPE tips are held in a rack, typically with sample pre-loaded onto the tips, and a robotic system moves the tips from the rack to a receiver connected to the head of the LC column. A capillary or other solvent delivery member is positioned in a first open end of the tip and the second open end of the tip makes a seal with the receiver such that in operation a solvent is flowed by means of a pumping system in a fluid-tight manner from the capillary through the tip to transport sample from the sorbent downstream to the LC column.
A problem with such automated systems is that they are not completely reliable and robust. For example, it is possible for the robotic system to fail to pick up a tip, or fail to pick up a tip correctly. In addition, it is possible that a tip that has been picked up may be dropped before it is connected to the LC system. Sometimes the automated system may use a tip that is damaged or otherwise unfit for use, for example since it has already been used. Attempted use of the system when such events occur may cause damage to the system or at least lead to spurious results. An aim of the invention is to address such problems.